介孔二氧化硅纳米颗粒结合神经干细胞构成靶向光敏药物运输载体用于肿瘤治疗  

A targeting photodynamic drug vehicle composed of neural stem cells and mesoporous silica nanoparticles for tumor therapy

作　　者：张卫佳[1] 陈家树 Zhang Wei-jia;Chen Jia-shu(Xinhua College of Sun Yat-sen University,Guangzhou 523145,Guangdong Province,China;Pharmacy School of Sun Yat-sen University,Guangzhou 510006,Guangdong Province,China)

机构地区：[1]中山大学新华学院,广东省广州市523145 [2]中山大学药学院,广东省广州市510006

出　　处：《中国组织工程研究》2018年第6期883-888,共6页Chinese Journal of Tissue Engineering Research

摘　　要：背景:神经干细胞对肿瘤细胞没有显著促生长作用,并且其可突破血脑屏障将药物运送到颅内肿瘤组织,目前神经干细胞被大量用于肿瘤药物靶向运输载体研究。目的:利用介孔二氧化硅纳米颗粒结合神经干细胞形成一个杂合的药物运输载体,探讨该载体是否能够用于光能药物靶向运输。方法:将光敏药物-酞菁锌包裹于介孔二氧化硅纳米颗粒中。(1)细胞吞噬实验:采用含不同质量浓度(0,10,50,100,200 mg/L)载酞菁锌介孔二氧化硅纳米颗粒培养液培养神经干细胞6 h,采用荧光显微镜观察细胞内颗粒;(2)细胞毒性实验:采用含不同质量浓度(0,10,50,100,200 mg/L)载酞菁锌介孔二氧化硅纳米颗粒(或单纯介孔二氧化硅纳米颗粒)培养液分别培养神经干细胞6 h,再常规培养3 d,MTT法检测细胞增殖;(3)纳米粒子细胞内滞留时间实验:采用含100 mg/L介孔二氧化硅纳米颗粒的培养液培养神经干细胞6 h,再常规培养12,24,72 h,利用荧光显微镜观察细胞内颗粒;(4)体外激发细胞内药物实验:采用含100 mg/L载酞菁锌介孔二氧化硅纳米颗粒(或单纯介孔二氧化硅纳米颗粒)培养液培养神经干细胞6 h,再常规培养12 h,以激光照射细胞,利用显微镜观察照射前后的细胞形态;(5)肿瘤细胞杀伤实验:采用含100 mg/L载酞菁锌介孔二氧化硅纳米颗粒培养液培养神经干细胞,再加入乳腺癌细胞MCF7共培养12 h,以激光照射细胞后继续培养12 h,通过荧光显微镜观察细胞死亡情况。结果与结论:(1)神经干细胞胞质中有纳米粒子存在,并且随着纳米粒子质量浓度的增加,细胞吞噬的纳米粒子量也增加;(2)对于有或没有包裹酞菁锌的纳米颗粒,在质量浓度小于100 mg/L时,对神经干细胞活性无明显影响;(3)培养72 h后,仍然有相当数量的纳米粒子聚集在细胞内;(4)载酞菁锌介孔二氧化硅纳米颗粒培养的细胞,激光照射后细胞膜发生明显破损;(5)载酞菁�BACKGROUND:Neural stem cells(NSCs),which exert no promoting effect on tumor growth and break through the blood brain barrier to deliver drugs into tumor tissues,are considered as a promising tumor targeted drug delivery vehicle.OBJECTIVE:To develop a hybrid delivery system composed of NSCs and moseporous silica nanoparticles for photosensitizer delivery,and to test if the system can be used for tumor therapy.METHODS:The photosensitizer,zinc phthalocyanine,was encapsulated in mesoporous silica nanoparticles.(1)Cytophagy experiment:NSCs were incubated with mesoporous silica nanoparticles(0,10,50,100,200 mg/L)loaded with zinc phthalocyanine for 6 hours,and fluorescence microscope was employed to observe the nanoparticles inside the cells.(2)Cytotoxicity test:NSCs incubated with mesoporous silica nanoparticles at various concentrations(0,10,50,100,200 mg/L)which loaded with or without zinc phthalocyanine for 6 hours,followed by 3 days of normal culture.Then,the cells were harvested for MTT assay.(3)Retention of nanoparticles within the NSCs:100 mg/L mesoporous silica nanoparticles loaded with zinc phthalocyanine were co-cultured with NSCs for 6 hours.Then,the cells were normally cultured for 12,24,and 72 hours,and observed with fluorescence microscope.(4)Zinc phthalocyanine excitation in vitro:100 mg/L mesoporous silica nanoparticles loaded with or without zinc phthalocyanine were co-cultured with NSCs for 6 hours.The cells were then normally cultured for 12 hours and irradiated with laser.Microscope was employed to observe cell morphology.(5)Tumor cell killing experiment:NSCs cells were cultured with 100 mg/L mesoporous silica nanoparticles loaded with zinc phthalocyanine,then mixed with MCF7 cells for 12 hours,and irradiated with laser.After that,the cells were cultured for another 12 hours and cell death was observed under fluorescence microscopy.RESULTS AND CONCLUSION:(1)After co-cultured with the cells for 6 hours,nanoparticles could be found in the cytoplasm and the number was increased with the concentration o

关 键 词：二氧化硅 神经干细胞 肿瘤 组织工程 

分 类 号：R318[医药卫生—生物医学工程]